Significance: Hypoxic ischemic encephalopathy (HIE), one of the most serious birth complications affecting full term infants, occurs in 1-2 per 1000 term infants, and 40-60% of these infants either die by age 2 years or have severe long-term disabilities including mental retardation, epilepsy, and cerebral palsy (CP). In the past, there were limited options for treating HIE. Currently, several experimental treatments are available to reduce the consequences of HIE, but outcomes of the treatments are uncertain and the treatments have side effects. Infants with HIE pose unanticipated challenges for parents and healthcare providers because the infants generally have had normal ultrasounds, no complications before delivery, and a normal birth weight. While the diagnosis of HIE cannot be made immediately in the delivery room, infants who later develop HIE may experience cardiac and respiratory distress at birth and require resuscitation. Determining how long to continue resuscitation is the first decisions. If the infant survives resuscitation, other decisions during hospitalization may include whether to treat the infant in a neonatal intensive care unit, whether to use experimental treatments, when to wean therapy, what types of technological support the infant will need, and whether to transition to end-of-life care. Following hospitalization, parents and providers may need to determine the specific needs of the infant including additional technological support and what developmental and physical therapies, and when to seek additional medical treatments for neurological and physical disabilities. Methods: This prospective, longitudinal, multiple case study will examine how decision-making trajectories of parents and providers caring for infants with HIE from birth to 6 months of age. To further illuminate how decision-making for infants with HIE develops, the decision-making trajectories for infants with HIE will be compared to those with infants with other complex life-threatening conditions: extremely premature infants (<26 weeks gestational age) and infants with complex cardiac defects (e.g., single ventricle) from an ongoing study (2008-2013, 1R01-NR010548). The comparison groups will be used to search for influences that optimize decision-making. The proposed study will provide information to develop interventions to aid parents and providers in decision-making for infants with HIE.